Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I

Monia Draghi, Nobuyo Yawata, Michael Gleimer, Makoto Yawata, Nicholas M. Valiante, Peter Parham

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Natural killer (NK) cells activate quickly in response to pathogens, tumors, and allogeneic hematopoietic cell transplants. Modulating the NK cell response are clonally distributed NK cell receptors that survey cells for change in the expression of major histocompatibility complex (MHC) class I and structurally related ligands. Here the enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine staining (ICS), and short-term culture were used to quantify the response of bulk NK cell populations from human donors to HLA class I-deficient 221 cells and to 221 cells transfected with single HLA class I allotypes. NK cells in cultures containing interleukin-2 (IL-2) or IL-12 exhibited specificities of HLA class I-mediated inhibition that correlated well with those previously defined using NK cell clones in long-term culture and with the frequencies of cells expressing particular inhibitory HLA class I receptors. Culture with IL-12, but not IL-2, gave an increased frequency of cells expressing CD94: NKG2A but no change in killer immunoglobulin-like receptor (KIR) expression. For some heterozygote combinations of KIR3DL1 alleles, ICS can be used to compare the functional properties of the 2 allotypes. Thus, both the low-expressing KIR3DL1*005 and the high-expressing KIR3DL1*002 gave similar inhibitory response on challenge with an HLA-B*5801 ligand. The single-cell assays developed here should facilitate future population study and clinical analysis of human NK cell regulation by MHC class I.

Original languageEnglish
Pages (from-to)2028-2035
Number of pages8
JournalBlood
Volume105
Issue number5
DOIs
Publication statusPublished - Mar 1 2005
Externally publishedYes

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Single-Cell Analysis
Natural Killer Cells
Cells
Interleukin-12
Cell culture
Interleukin-2
Assays
Clone cells
KIR Receptors
Natural Killer Cell Receptors
Cytokines
Ligands
Transplants
HLA-B Antigens
Pathogens
Major Histocompatibility Complex
Tumors
Staining and Labeling
Enzyme-Linked Immunospot Assay
Enzymes

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I. / Draghi, Monia; Yawata, Nobuyo; Gleimer, Michael; Yawata, Makoto; Valiante, Nicholas M.; Parham, Peter.

In: Blood, Vol. 105, No. 5, 01.03.2005, p. 2028-2035.

Research output: Contribution to journalArticle

Draghi, Monia ; Yawata, Nobuyo ; Gleimer, Michael ; Yawata, Makoto ; Valiante, Nicholas M. ; Parham, Peter. / Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I. In: Blood. 2005 ; Vol. 105, No. 5. pp. 2028-2035.
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